Pyrrolizidine alkaloids have attracted considerable attention because of antitumor activity associated with certain members and because of the increasing number of deaths to livestock attributable to consumption of plants containing pyrrolizidine alkaloids. If the proposed chemistry involving the diene-nitrene synthetic equivalence is successfully developed, then we would be able to prepare a wide variety of necine bases common to the pyrrolizidine alkaloids. Methods involving the ring expansions of 2-azidoalkyl-2-cycloalkenones should provide generally useful routes to indolizidine, pyrrolizidine and quinolizidine ring systems. These substructures are present in a wide range of medicinally useful alkaloids; we will attempt to synthesize lycopodine to determine if reasonably complex alkaloids can be constructed by our strategy. These same ring expansion processes should be applicable to synthesis of the important antibiotic group, the Beta-lactams. We will begin by developing a novel total synthesis of penicillin G and work towards a strategy for modified penicillins, cephalosperins and the new generation bicyclid Beta-lactam antibiotics such as thienamycin. New directions in polyquinane construction should provide a total synthesis of the cytotoxic sesquiterpene pentalenolactone. Our goal is to develop general and enantioselective methods for the synthesis of polyquinanes. Finally, exploratory research on the concept of intramolecular cycloadditions to photochemically generated zwitterions could provide a conceptually new strategy for the construction of complex ring systems.